Does the addition of recombinant LH in WHO group II anovulatory women over-responding to FSH treatment reduce the number of developing follicles? A dose-finding study.
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BACKGROUND: In anovulatory women undergoing ovulation induction, addition of recombinant human LH (rLH) to FSH treatment may promote the dominance of a leading follicle when administered in the late follicular phase. The objective of this study was to find the optimal dose of rLH that can maintain the growth of a dominant follicle, whilst causing atresia of secondary follicles. METHODS: Women with infertility due to anovulation and over-responding to FSH treatment were randomized to receive, in addition to 37.5 IU recombinant human FSH (rFSH), either placebo or different doses of rLH (6.8, 13.6, 30 or 60 microg) daily for a maximum of 7 days. The primary efficacy endpoint was the proportion of patients who had exactly one follicle > or = 16 mm on hCG day. RESULTS: Among 153 enrolled patients, the five treatment groups were similar in terms of baseline characteristics. The proportion of patients with exactly one follicle > or = 16 mm ranged from 13.3% in the placebo group to 32.1% in the 30 microg rLH group (P = 0.048). The pregnancy rate ranged from 10.3% in the 60 microg group to 28.6% in the 30 microg rLH group. Adverse events were similar between groups. CONCLUSIONS: In patients over-responding to FSH during ovulation induction, doses of up to 30 microg rLH/day appear to increase the proportion of patients developing a single dominant follicle (> or = 16 mm). Our data support the 'LH ceiling' concept whereby addition of rLH is able to control development of the follicular cohort. (+info)
Predictors for treatment failure after laparoscopic electrocautery of the ovaries in women with clomiphene citrate resistant polycystic ovary syndrome.
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BACKGROUND: Laparoscopic electrocautery has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). In order to make an informed treatment decision it would be helpful if we could identify women with PCOS with a high probability of treatment failure following electrocautery of the ovaries. METHODS: Eighty-three women with CC-resistant PCOS were allocated to receive laparoscopic electrocautery followed by CC when anovulation persisted as part of a randomized controlled trial. Multivariable logistic regression analyses using clinical, ultrasonographic and endocrinological parameters were performed to predict (i) failure to ovulate within 8 weeks after electrocautery, and (ii) failure to reach an ongoing pregnancy after electrocautery with or without CC. RESULTS: Of the 83 women, 56 (67%) ovulated within 8 weeks after electrocautery. The model for predicting anovulation after electrocautery included LH/FSH rate, year of menarche and glucose level. Women who were younger at menarche, had a lower LH/FSH ratio and a lower glucose level were more likely to have persistent anovulation. The area under the curve was 0.74. After electrocautery and CC, 41 women reached an ongoing pregnancy. No prognostic parameters could be identified to predict failure to reach an ongoing pregnancy after electrocautery followed by CC. CONCLUSIONS: Persistence of anovulation after electrocautery could be predicted and women with a high risk of persisting anovulation could be distinguished. We were, however, not able to predict treatment failure after electrocautery followed by CC. (+info)
Effect of anovulation factors on pre- and postmenopausal ovarian cancer risk: revisiting the incessant ovulation hypothesis.
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Risk factors for ovarian cancer may differ between pre- and postmenopausal women. The authors used data from a multiethnic, population-based, case-control study, conducted between 1993 and 1999 in Hawaii and Los Angeles, California, to examine whether menopause modified the effect of ovulation on ovarian cancer risk. A structured questionnaire was administered to 558 histologically confirmed epithelial ovarian cancer cases and 607 population controls. Lifetime ovulatory (log)years were significantly associated with an increased risk of ovarian cancer (odds ratio = 1.78, 95% confidence interval: 1.24, 2.57), particularly among premenopausal women (odds ratio = 2.49) but not among postmenopausal women (odds ratio = 0.88) (p(interaction) = 0.006). Factors that induced anovulation, including oral contraceptives, pregnancy, and breastfeeding, were associated with a reduced risk of ovarian cancer. Among anovulation factors, prolonged oral contraceptive pill use provided a greater protective effect against premenopausal ovarian cancer than against postmenopausal ovarian cancer (for > or =5.4 years of use vs. never use: odds ratio = 0.28, 95% confidence interval: 0.15, 0.52 vs. odds ratio = 0.58, 95% confidence interval: 0.31, 1.08, respectively), but the difference was not significant (p(interaction) = 0.20). Association of breastfeeding and pregnancy with ovarian cancer risk was also similar between pre- and postmenopausal women (respective p(interaction) = 0.72 and 0.43). The authors' data support the hypothesis that lifetime ovulation is involved in the pathogenesis of pre- but not postmenopausal ovarian cancer, while the protective effects of anovulation factors persist from pre- to postmenopausal women. (+info)
Does metformin modify ovarian responsiveness during exogenous FSH ovulation induction in normogonadotrophic anovulation? A placebo-controlled double-blind assessment.
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OBJECTIVE: To assess whether the addition of metformin to gonadotrophin ovulation induction in insulin-resistant, normogonadotrophic, anovulatory women alters ovarian responsiveness to exogenous FSH. DESIGN: Placebo-controlled double-blind assessment in an academic hospital. RESULTS: After a progestagen withdrawal bleeding, patients were randomised for either metformin (n = 11) or placebo (n = 9) treatment. In cases of absent ovulation, exogenous FSH was subsequently administered to induce ovulation. Only during metformin treatment did body mass index and androgen (androstenedione and testosterone) levels decrease, whereas FSH and LH levels increased significantly. In the metformin group, a single patient ovulated before the initiation of exogenous FSH. Significantly more monofollicular cycles and lower preovulatory oestradiol concentrations were observed in women receiving FSH with metformin compared with FSH alone. CONCLUSIONS: Metformin co-treatment in a group of insulin-resistant, normogonadotrophic, anovulatory patients resulted in normalization of the endocrine profile and facilitated monofollicular development during the FSH induction of ovulation. (+info)
Irregular cycles and steroid hormones in polycystic ovary syndrome.
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BACKGROUND: This cross-sectional study was undertaken to evaluate the factors that relate to menstrual status (oligo-amenorrhoea versus eumenorrhoea) in polycystic ovary syndrome (PCOS). METHODS: A total of 234 women with clinical and biochemical features suggestive of PCOS underwent metabolic and hormonal evaluation. A forward stepwise logistic regression model was created based on the results to determine variables related to ovulatory status. RESULTS: Only follicular phase progesterone and estradiol (E(2)) were retained in the final model. This model correctly classified 80% of PCOS women by ovulatory status. Univariate analysis revealed no difference in progesterone between ovulatory groups but E(2) was higher in anovulatory groups. This suggested interaction between progesterone and E(2) and the single interaction variable (progesterone/E(2)) also classified 80% of women by ovulatory status correctly. CONCLUSION: The results suggest that a low ratio of progesterone to E(2) is associated with menstrual irregularity and ovulatory status in PCOS. (+info)
Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).
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BACKGROUND: Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. METHODS: Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. RESULTS: The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. CONCLUSIONS: The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped. (+info)
A case of ovulatory cycle-dependent symptoms in woman with previous interferon beta therapy.
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A woman with a menstrual cycle-dependent fever (more than 38 degrees C) and severe fatigue that disrupted her ability to work was referred to our hospital. Six years ago, the patient received interferon beta injections (6,000,000 IU day-1x48 days) for the treatment of hepatitis C virus. Although the treatment was successful against the virus, the symptomatic fever occurred monthly since the third year after receiving the treatment. The symptoms occurred a few days after ovulation in every menstrual cycle. When the ovarian function was suppressed by GnRH agonist (GnRHa), the symptoms disappeared. While in anovulation, the patient received estrogen followed by estrogen with progestogen, which resembles the sex hormone milieu of a normal menstrual cycle without the LH surge; this treatment did not induce the symptoms. When human CG (hCG) was injected on the beginning day of estrogen with progestogen following treatment with estrogen alone, the previous symptoms reappeared. However, the hCG injection without estrogen priming did not induce the symptoms. These studies indicated that the LH surge after estrogen priming induced the symptoms. Changes in serum inflammatory cytokine levels (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) were examined during the ovulatory cycle and the interleukin-1 levels during the treatment. There were no significant changes on these levels in the febrile period. The patient experienced normal menstrual cycles after finishing the five-month GnRHa treatment. Although her symptoms still occur, they are mild and do not require further medical treatment. (+info)
Hyperprolactinemia after laparoscopic ovarian drilling: an unknown phenomenon.
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BACKGROUND: The effects of ovarian drilling on the serum levels of gonadotropins and androgens have been studied previously. The aim of this study is to evaluate the effects of ovarian drilling on the serum prolactin levels and its relation to ovulation in women with polycystic ovary syndrome. METHODS: This is a prospective controlled study. Thirty-six women with PCOS underwent ovarian electrocauterization in university hospitals. Control group consisted of 35 ovulatory women with unexplained infertility. Hormonal assessment performed in early follicular phase of spontaneous or induced cycle before operation in the two groups and repeated one week after operation. Hormonal assay was also performed in the early follicular phase of the first post-operative menstruation, folliculometry and progesterone assay were also performed in the same cycle. Data were analyzed by "repeated measurement design, discriminant analysis, correlation coefficient, and Fisher exact test". RESULTS: Six to ten weeks after operation the serum mean +/- SD prolactin levels increased from 284.41 +/- 114.32 mIU/ml to 354.06 +/- 204.42 mIU/ml (P = 0.011). The same values for the control group were 277.73 +/- 114.65 to 277.4 +/- 111.4 (P = 0.981) respectively. Approximately 45% of subjects in PCOS group remained anovulatory in spite of decreased level of LH and testosterone. Prolactin level remained elevated in 73.2% of women who did not ovulate 6-10 weeks after the procedure. CONCLUSION: Hyperprolactinemia after ovarian cauterization may be considered as a possible cause of anovulation in women with polycystic ovaries and improved gonadotropin and androgen levels. The cause of hyperprolactinemia is unknown. Hormonal assay particularly PRL in anovulatory patients after ovarian cauterization is recommended. (+info)